Investigation into the immunologic etiology of some human uveitides has necessitated the development of animal models. Primary attention has been given to the experimental allergic uveitis (EAU) induced by retina extract containing S-antigen. When given in low doses, purified S-antigen can produce a uveitis that is histopathologically similar to that seen in humans exhibiting sympathetic ophthalmia. The experiments of this application are designed to characterize the immune response involved in EAU as well as to define and evaluate several models of EAU. A thorough description of the immune response involved in EAU is vital to relating the animal studies to human uveitides, especially to defining those specific components of the immune response to be measured for diagnosis and/or evaluating the patient's progress. Specifically we will characterize the various components of the immune response in S-induced EAU by measuring both humoral (antibody) and cell mediated immunity at both the local (ocular) and systemic levels. Once these components of the immune response have been defined in the rapid onset, severe response to retina extract, studies of the response to low doses of S-antigen and to other autoantigens will then be more feasible and economical. We will continue to study the autoimmune response of uveitis patients by examining sera and peripheral leukocytes for anti-ocular activity. Since these techniques measure a systemic immune response, results from the above described animal experiments should then allow us to assess the local immune response in the eye as reflected in these systemic measurements. We will also define and characterize additional models of EAU that are similar to human uveitides of immunological etiology and of these autoantigens and their corresponding immune responses is essential for distinguishing different models of EAU and for relating different models to human uveitides.